Effect of buccal dwell time on the pharmacokinetic profile of fentanyl buccal tablet

Abstract

Background: The time fentanyl buccal tablet (FBT) takes to completely dissolve after placement on the buccal mucosa (i.e., ‘dwell time’) could exceed the time to onset of analgesia. Objective: To examine the relationship between FBT dwell time and fentanyl pharmacokinetic parameters. Research design and methods: This was a post hoc exploratory analysis of data from two randomized, open-label, crossover, pharmaco�kinetic studies that were designed to assess dose proportionality within the anticipated therapeutic dose range. Healthy adults received single FBT doses of 200 – 1080 μg in Study 1 (n = 28) and 270 – 1300 μg in Study 2 (n = 42). Main outcome measures: Assessments included buccal dwell time, defined as the duration of FBT presence in the oral cavity, and the following pharmacokinetic measures: maximum serum concentration (Cmax), time to Cmax (Tmax) and area under the concentration–time curve (AUC; exposure) from 0 minutes to median Tmax adjusted for the dose (Tmax′) (AUC0 – Tmax′). Spontaneously reported adverse events were recorded. Results: Mean buccal dwell time for FBT across the dose range varied from 14 to 25 minutes (range 3 – 62 minutes). There was no evidence of an association between FBT dwell time and values for Tmax (medians 45 – 60 minutes), dose-normalized Cmax (means 0.42 – 0.66 pg/ml/200 μg) or dose-normalized AUC0 – Tmax′ (means 0.24 – 0.38 pg·h/ml/200 μg) over the range of FBT doses delivered. All adverse events reported were mild to moderate; none were unexpected or serious. Conclusion: The pharmacokinetic parameters of FBT did not appear to be related to its buccal dwell time.